February 9,2 c ment Branch WA-309

02/10/2000
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February 9,2
c
ment Branch WA-309
Association (NM) appreciatesthe opportunity to comment on
nt on the Human Health Impact of F’luoroquinolone Resistant
e Consuznprionof Chicken.” It is our understanding
type of risk assessmentto determiae the feasibility of
resistant foodborne pathogensassociatedwith the
ng animals, including aquaculturedanimals. The
e tndustry trade associationwith over 2000 members We represent
ulture industry wztors (species) involved in the production of over 35
be considerablemisinformation about the role of US aquaculture in the
cterial pathogens- Part of this misinformation
lack of data germaneto the US aquacultureindustq regarding the
the environmenf the causes of antibiotic resistanceunder
ns, and the probability of resistancetransfer fiorn aquatic bacteria to
is also porn understandingabout US aquahre practices. For
at antibiotic resistancecan occur under aquacuhureconditions
lotrc use. This is believed to occur as a consequenceof high
ens- We suggestthat there are severalnaturai barriers that make
CESa very low risk to human health. We summarize below some of the
the risk assessmentmodel and provide more extensive rraalysisof the
ante issuesand US quaculture in the attachedmemo f&n tbe NAA
Health Committee.
challengesto using the draft model for e&mating
aquatic animals are minor speciesrelrrtive to human
of the amount of human wosllmption of
compoundedby the tack of evidence
iated with f&me
diseases. With the
111 West Washington Street, Suite 1
Charles Town, WV 25414-1529
Tel. 304/728-2167 Fax. 304/728-2196
Email: [email protected]
.
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02~10~2000 09:4a
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sh and salmonids, per capita consumption data is not readily
quaculture Census(I 998) identified 35 speciesunder
the US Many ofthese are food animals akhough most ofthese
e to use antibiotics becausetherapeuticsare not approverifor use
uatic animals have not been implicated in foodborne diseases.We
s for this. Fin&h and shellfish are poikilothermic animals. As
in or on these animals does not commonly occur in people or
There are no residentbacterial speciesin fin or shellfish. Bacteria
r on the feed might occur in or on the fish but these are readily
Thus, Campylobacterje~i
has not been reported on any f&m
ies. Zoonotic bacteria are rare in most aquatic animals
. Certain warm water speciesof farm raised aquatic animals (e.g.
ated with possible foodbome pathogens(e.g. IblmoneZ~ or
8sefrom 8quaculturedafinds have been associatedwith human
the US Cool and cbld water farm raised aquatic speciesrarely if
evels of human pathogenson the fish Gllets. The FDA monitors the
in seafoodand in their latest report (DCIEP 98-12) rhey
% of their samples. Ofthe eleven positive mples, four
cultured ca@sh,four were imported shrimp (two of which
e inrported aquaculturedtilapia and one rumple was a wild
er speciestested included trout (aquacultured), salmon
haddock (wild), perch (wild), po&ck (wild), sole (wild), and scallops
not be determined ifthe Wmonella occurred f5om human contamination
essing. Listeria monoqytogenes hasbeen identified in trout from
not beerrdetectedin trout from Idaho. Idaho produces60-75% of ah
s in contrastto reports from other countries
In somecountries, human sewageor terrestrial
to rearing waters to increaseprimary (algal)
production There are severalreports
could be associa@dwith human foodborne
there is someuncertaiuty asto the accuracyof these reports. In the US,
sefidly added to rearing waters. It is also not clear whether
occurred before or afI= fish processing. Shellfish
e been associatedwith f-me
disessebut these
r open water conditions and do not receiye antibiotics in
purposesin US aquaculture. This differs from at
practices. In the US, only two antibacterial
ne and the potentiated sulf&unide, Romet-30) are approved and
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and lobster) aquatic food animal production.
countries use up to 29 antibiotics or combinations in their aquaculture
sk assessmentmodel for determining risk to human health from
gens associatedwith the use of antimicrobials in US
is highly questionable. US consumption patterns do not
sufficient data and the diversity of aquatic animals raised
enceof human pathogensin fanm raised
sociation of Wborne illness with
s IS non-existent. Thus there would be
ch to utilize this model for assessingthe risk of aquacultu~~to
e suggestupriovi that US aquacultureis a very low risk to buman
ation ofthe attacheddocument to help formulate the best means
t-4 with the use of acltibiotics in US aquaculture.
Sincerely,
oh-nR MacMill~
President
Encl.
Ph.D.
02/10/2000
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NATIONAL AQUACULTURE ASSOCIATION
ONE
INDUSTRY
- ONE
VOICE
Memorandum
Date:
From:
D
N
mber20,1999
Aquatic Animd Health Commiztee
Subject:
‘ew of Dr Fred Angulo’s memo, October 18, Is)99titled: USEof antimicrobial
in aquacultture:potemial for public health impact.
aag
Thisisarevkw
Fred Angulo’s analysis (attached)of the scientific literature regarding the
impact ofthe use of antimicrobial agentsin quacukre. Fred Angelo is a
with the National Center for k&ctious IXwues, Centersfor Disease
). The National Aquaculture ASBoCistioahad challenged the
nus aquaGlJ.ltllre
pniaices powi 8 !iiigrLifiaifnrisk to public
pees reviewed jourmls
in its attempt
ably beww there is m substantive
public heah& The CDC analysis made gross
in order to apporc their position. in at 1eaJtone
the scientik literanne. CDC did not cite any evidence of problems
US aquacukwe practicesbux instead relied on tilat~ inWnW
dly examine scientific IitczMure rhat
for aquatic bacteria that danonstrare
ntwte US aquachure prdces hmthose
aedoesaotappearto~aayr~~~onfbrthediffaPncesintlnt
procwiotkluscomparedtoo&ermrmtries.
Theredoesaotappear
for difkences in hygiene between cow&e and thesedifferencts create
cchumaahealth. TheredoeanotappeartobeanyIPcognition~rthe
to otb cmmtries. Al3 of these Gctas
cmae abarrier to r&awe trawfkr and could substantially impact relative risk.
111 West Washington Street, Suite 1
Charles Town, VW 25414-l 529
Tel. 3M28-2167
Fax. 304fi’28-2136
Email: [email protected]
WlQfl2
02/10/2000
09:48
conditions to se
Tbffe are sevd
documentedthat
resistant bacteria
TheCDCdidn
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otential for antimicrobial use under aquaculture
an antibiotic. This is in agreementwith UlideIy
evidence that antimicrobial use of any extent in any environment is likely
resismnt bacteria in whgtenvironment (e-g Obrien et al. 1987; Coucol et
993; LesviS1995; Gaynes 1997; Levy 1997; Cfistino 1999). Most
antibiotic resistancedevelopment in the human hospital settiag
this environment have been iden.ti&d (Gaynes and Monnet 1997).
the international and US scienti& literature dexribing the
eria follting use of antibiotics for therapeutic purposesin
s et al. 1989; Cooper et al. 1993; Stariiper 1993). Antibiotic resistance
in bacteria abrained&om wild fish Ptibone et al. (1996) isolated
&ant Aerwmonas spp. fiorn wild brown bullhead (1~~2~~ nebulosus)
o Riw in New York The assumption in this researchwas that
n of the BufGlo River with antibiotics 6rom sewageout&& led to tbe
resistant -monads
that could infect or colonize fish Sewed others
w and Prozesky 1973; Baya et al. 1986, and Hirsch et al- 1999) have
iotics or antibiotic resistant bacteria urn ocax in sewage. Antibiotic
also occur in the apparentabsenceof antibiotic use. Baya et al. (1986)
fiam clean water open ocezmsites were resistantto penicillin
mycia. Spanggaardet al. (1993) noted 6% of bacterial isolates
stmam in Denmark were resistant to oxytetraqcline. The factors
ence of antibiotic resistancein the absenceof antibiotic use were not
ear&I consideration. McPhearsonet aL (1991), Kaperaztakiet al. (1995),
feport that other fistors such asrelatively high levels of nutients con
e fkqumcy of resistantbacteria in aqua& environments- These
tolerant ofantibiotic becauseof membrane mediated re&ance (Smith et al.
mid mediated and occurs even in the absenceof mtiiiotics.
More recedy
R a ipificam
leve1 of anti&tic resistantEnteroiwrrer from wild
nment fizz of antibiotics attributed to human usage. The f&ors
of this resistanceare also unknown
evaluate diffkrences in resistancebreakpoints amom rhe tie&c
this may have been beyond the scopeof their assignment the issue
matiaa. The dangerof assuming all literature published is relevanr and
was recently illustrated by Ewert (1998). Ewert (1998) compared
sedby the United Kingdom’s Labor&q ofEntefic Pathogens(LEP)
Committee for Clinical L&oStandards
ciprofloxacin. The LEP breakpo& is 0.25 @ml
is 4 p&l. Clearly, international standardiz3tion of resistance
about public health risk are to be made- Such analysis of the CDC
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were isolated fro
even ar the refer
collectd 20 m
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bat resistancecan occur among aquatic bacteria rhat are
The evidencecited above supports this. However, the CDC analysis
will not occur in areasnot subjectedto antibiotic use. This is incorrect as
al. 1986; Spanggaardet al. 1993: and Gilliver et al. 1999). The
cited (Em& et al. 1994) is in error. Ervik et al. (X994) did not
in fin fish from untreated areasas
were in fact examined up to 500 m away
greater prevalenceof resistant bacteria
to the farvl but resistancewas still detectable
station Factars accounting for resistancedistant from the fish farm were
to factors independentof antibiotic use (Mcphearson et al.
ughn et al. 19%; and Smith et al. 1997). EMk et at (1994) did
of oxolink acid and flurnequine antibiotics in blue mussel and wild
Highly variable concentrationswere deteceedranging from 0.95 to
more extensive examination of blue mussels,Coyne et al. (1997)
of oxytetracycline. Oxytetracyciine was not detectedin rnusseIs
et pen. Coyne et al. (1997) observedsignificant conczr&ations of
s but the presencewas extremely transient and tiied
musselswere
ate proximity ofthe cages. These authors suggestedthat the most prudent
tentiaI human health risk was to educatetkm personnelas to the risks.
rehin from eating musselsobtain& fiorn the inundate vicinity of tbe net
obial resistant bacteria occurkg in aqwzuke
ftiors to other bacteria but how fkqumtfy this occurs in
believe a similar transfer can occclrfrom other bacteria to
s, under artificial environmemg Kruse and
ed that resistanceplasmids could be transferred from the human
to the fish pathogenAeromdm ~&~.Gicicdo and from a bovine E coli
What is not clear is how successfulsuch transfer would be uuder ~~III
&rum (1994) used simulated natural environments and comrokd
attempting to answerthis question. Factorsthat may influence the transfer
fsbaring
the same environment,,
bacteriaI abundanceand
srudy is required if the significancr?of suchtransfer potential
c bacteria is to be properly
ility ofthis CXcWrmg.At leasesome
s not tzansf’erable(Weal et al. 19%;
ames et al. 1990).
.
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I
The CDC analysis rrectly idemified a possibQ&
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of the transmission of bacteria present under
is unique in that zoonotic btitia are rare in most aquatic animals. The
the fictors accounting for such transfer when it did occur, which is
le become infected with bacteria present in or on fish and theseare
conditions of poor hygiene or umsurnption of raw products. Fish are
s such that &w bacterial pathogensof farmed fish in temperate climates
humans (Alderman and Hastings 1998). Rarely can even warm water
bacteria occur in humans. Thus, there are isolated reports of various
sh and humans; for exampleAepomoms hyckoptilcr, &harc&ieielh
shgelloidw, and S~eptococcus inirre (Smith et al. 1994; Weinstein et al.
arive frequency of such inftiions in humans apponrslow, they can occur.
ed in personnel involved in the processingof Tifcpha but has not
detection CDC describesa scenariothey believe suggeststhat
iotic resistant fibrio cholera occutred becauseofthe tcan&r of
mEcuador shrimp farms. While
is unknown and likely very
epidemiologic casecontrol
1risk favors for infectida that included
arninaredwater, drinking a beveragefrom a street vendor, eating raw
oked uab (Weber et al. 1994). These risk fh.ctorssuggestpoor hygiene
or in the Ecuador cholera epidemic. Another possibibty, for example, is
of antibiotics in Ecuador are not well regulated for shrimp or for humans.
se of anthiotics could promote occurrence of antibiotic resistant V: cholera
matter and smvage- Subsequentdisposal of sewagecould contamiaate
workers. Antibiotics used in Ecuador for humansor for shrimp may also
p3iUliUi~COlJld
ividuals handling live ISpia
and Raz 1996). In the Israeli incident, %piu were
eutha&ed. Subsequenthandling of the live Bsh
nts of the iW@a. The souru~of the bacteria
been bacteria carried by live Tihpiu. PRY- fid
minimizing food borne illness. In Israel, when the fish
ctione cased to occur (Bisharat and Raz 1996).
are nomal bacterial flora in the marine environment @IYIUNI et al.
ecred&at fish obtained from that environment would have thesebacteria
appropriate to assumeinfections could occur again if live fish are not
roper bandhng may have a significant impact on the prevalenceof food
met and Kass (1987) found very low prwalence of ir&tion with
cuii among female poultry ahattoir workers exposedto wnsidzrahle
dbiitic-i
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amouuts of antibic ic resistant bacteria. While not absolute protection, it seemsreasonableto
believe that washi g hands minimizes infections from poultry borne 5Wmorte2h and
C2mpykhcter as lees atcemionto good processingpractices and proper cooking. CDC fbrzher
cites xefkrwcc to 1 od borne diseaseTom V: parahemo&&~ infkcrions in Japanwhich were
IklkdtOfarmtiS
d finfish. Y,PcrnJlemoryrinL iufections may occur as the result of
consumption of ra I, improperly cooked or recontaminatedd
(Oliver and Kaper 1997)
Ccmsum~on of n v scdood in the United Statesis relatively rare (with the exception of raw
molluscs) but dam ocwr. CDC also cites isolation of srr/moraellcrf?om fkrm raised fish and
shrimp ponds. Sal muella are ubiquitous in the natural environment @‘Aoust 1997) bur
whether all specie or serovarscan causediseaseis unknown CDC implies but does not state
that the Sdwone2~
f5om krm raised fish environmcrrtscould causehuman disease- Certain
gwea arc required br &.I1virulence. For example, it is believed that the invasion gene operon,
imA, is essential in Sdmoneliiz ibr Fidelvirulence (Galan and Curtiss 1989). Salmonella
virulence is also a! ociated with a virulence plasmid spvC (Gulig et al. 1993) which is not
presentisail sak lella. Swamy et al. (1996) demonstratethat non-typhimurium 5WmoneZla
iaikcqucndy have he Lprvcplasmid. Bjkkman et al. (1998) found that most S. &m
mutauts~istautt
streptomycin, rifkmpicin, and nalidixic acid were a&lent in mice
thar
=SSestiagt)levW~ aid aiso be aviruleut in humans. It remains to be demobsdmonelh spp fit II fkrm raised fish or shrimp ponds might causehuman diseaseand if = under
what conditions.
In the United Stat 3 the US Food and Drug Administration monitors the occurrenceof
sblmoneflrl in scaf od.. In the B998 $bhuneZkr in Seafood Assignment (DOEP 98-12)
SummaIy, szlmon Ikr spp were detectedin 11 of 405 samplestested (2.7/o). Ofthelevec
cight.werefiumaf
mculturc oper&ons. All of these had been fix&r prmsscd to s~mc Went
sotheoriginofthg
abulldance of !WJ
LakshmaMpe!nlml
crustaceansfiomf
were isolated eon:
chloramphenicol a
resistancewas due
collntlies. Post-ha
smitary conditioru
SbbnuneZbspp- could not be asc+xtained.The seafoodwith the highest
me2k was from wild uaptured shrimp from India Hatha and
@my (I 595) sampled the prevalenceof SdLnoMk among fish and
UTmajor seafbod retsriloutlets in India A total of 240 &zkme& &rains
1,006samples(24%)). Oftbese, 9% were resistant to bacitxin, 73’0to
d 46% to ovacycline.
The authors conclude that the high prevalenceof
o the use of human wastewater in aquaculture industries of third world
rest conttinadon of produds might also a&e from processingunck poor
accordingto theseresearchers.
Tbec!Dcsmtestht “these and other reports indime that bacteria present in aquaculture
eamystems
ambe ransmitted to humans.” The implication of this statementis tkt there is
something
unique buts atpaculme ecosystems that promote the occurreuceofpoteatially
While there are indeed reports documenting the occurrencc of human
pathogensin aqua4 rlturc ecosystems,the ocwrren ce of actual human diseaseassociatedwith
theseenvironment is rare, No reports documenting that fish km workers have a greater
pr#Wak.lceofbact rial diseasethan those working in other emkonments couId be discovered.
pdlogfznic bactfai
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Review of CDC
Related DiseaseReports (St. Louis 1988; Levine et al. 1990) did not
document any
e outbreaks associatedwith US fish farms. The CDC does not cunwrtly
have a monitoring rogmm directed specifically at aquaculturefkciities or areas. Alderman and
Dastings (1997) ar e that the probability of pathogensearn fish farms af%xing humans is very
fOov~
definitive type 104 @T
line resistant ‘may have originated in aquaculture. The evidence fix this is
class G resistancegene that was first de&bed in isolates of K
en of fish CDC further speculatesthazthe novel florfenicol resistance
DT 104 came fkom Photobacttiriym (Fibrio?) &an&~, a bacteria
in marine environments. Theseargumentsare highly specularive.
e class of resistancegene in a fish pathogen for the first time may merely
beduetoafoti
of a particular isolate. Bolton et al (1999) statethat
(which is the SameasflorR) positive and that florfknkol
resisbmceis likely
found in other bacterial speciesif testing is done.
Boltou et al. (1999
est that it has not beenthe use of florfenciol in wtrle that accounts
selection of theflo,, geneotypebut rather other i’acors. The CDC
by the recent d&e&on of the class G teuacychne resistancegene
m Michigan apple orchardswith no or limited history of
Jones 1999). CDC stretch= credibility in speculating that
DT IoQflorR was from P. rkmLeelrr. The P. &m&
reported by
y referencedin theii memo) w probably cultured from wild fish not in
lture conditions (Love et aI- 1981). In contrastto CDC, Sriggs and
~thatDT104commanlyoccursincattIeandhasbeencontracced
WalI et al. (1995) provide evidencefor the transmission of S.
to mm Reports documenting the transmission
of S. trphimnium 6om
suggesting that Solmane~Za serotype ~phimwium
antimicro’lbialresistancederertninantsresulting from aqua4ture’s use of
pathogensat a 16requency
grater than previously suggested.
reiceutreviews (Smith et.al. 1994, Aldermaa imd Hastkgs
that the p&ability of antimicrobial resistanceoccuning in hurtwk
the use of antibiotics in aquacukureis low. These authors smtethat the
e trausfw in the US is even less than in other countries beceuseof the
process and the con&ions of use in the US. We add that animal
emeftt conditions practiced in the US thrther reduce probability of
f the aquaculmre praciiced in the US are dishwater basedand
the eflluent through w$tling ponds that capture solids.
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speculative and does not addressprobabie risk. The CDC review
does not difFerenti e between aquaculture in the US or in other countries.
Aquadre
practices
particuiarly regarding the use of antibiotics. In Japan
may be used (Okamoto 1992) and in Chile 16 17
In contrast, only two antibacterial drugs are approvk, available and used in
Y&xlfish industry. Antibiotics are not used in US aquacuhme as growth
promoters and are Ily applied for the treatment of catkin bacterid diseases. Considerable
rs in the type of water usedto cultivate aquatic auimals. In China and India
from human sewagemay be used. Kontara and Maswardi (1999) report
re is common in Indonesia. Integrated aquacultureoccurs when feeal matter
~QP-a-Jq
from a pouhxy open tion is deposited in a fish pond to fertilize the pond stimulating algal growth
fbr fish consumptid I. In the US,, this practice does not occur nor is sewageused as a sourceof
aquacuhurewat=- Vocessingstandardsare also substantially difkent. FDA recently instituted
a mandatoty seafbo Lpmcessor Wd
Analysis Critical Control Point program which provides
increasedassumnccthat only approved antibiotics are usedand not misused,and processedfish
are not likely to cot tin human pathogens.
CDC has not addm wd the issue of whether reduction in the use of antiiiotics in US iiquacutture
would make a signi icant difference in the prevalenceof antibiotic resistant human pathogens.
This is an importan: questjon becauseits answer would have great bearing on how bestto
addressthe use of a &ibiotics in US aquaculture. Couflicting reports, even in hospital settiugs
where successis mc st likely, make such a judgement diicuk One report (Crktiuo 1999)
suggestsreduction i t use of macrotides in Danish hospitals has led to a duxeaae in the
ptevaknce of enhrc nycin resistant SwWpmmse
Qhile this requires further
exploration and dot I not addressanimal sgri&ure or aquaculturew
other reports Gil to
substantiatethis obr nation. Two recent reports (Schraggand Penot 1996; and Levin et al.
1997) suggest reziut 5011in antibiotic use will have little impact on the prevalenceof resistant
bacteria AdiEiir
id impact between hospitals and other enviconmerrtsmight be expected
l-jcwalseof clifhzren~BSin dynamics. Over presc@tion of antibiotic in hospitals is one pot4
f&or- Hospitals 8rl also s&ject to considerablebacter%Jmigration as patienrs enter and leave
Such mignition and x#acement of bacterial populations could occur in an acceleratedfashion
becauseof roukle 9 ubtion that destroysresident microflora In contrast, outside the hospital,
such sanitarion pramices are unlikely to occur and changein microbial flora could be slower.
Other faaors likely :o &kct resistancegenetransfer probability are cell density and donorrecipient compatibi, ty- Considerably more ir&orma&onmust be available before informed
decisions can be m le.
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@Ill
T.S. Hastings. 1998. Antibiotic use in aquac&ure: development ofantibiotic
er health risks, Int. J. Food Scienceand ‘Technology. 33: 139-155.
Aryq SC. 1999.
biotic resistancein the twd Americas. ASM News 65: 585.
T.S. Hastings and S.G.B. Amyes. 1990. Cross resistancebetween
ic acid in Aemnontzs saimniciidrr associatedtitb outer membrane
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J-V. Lee. 1984. Genus l- Vibrio Pa&i 1854,421. In:
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D-1. Anderson. 1998. Virulence of antibiotic-resistant Sutionef&
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hnoneikt entericrr serotype jlphrinaium DT 104 basedon a genewhich
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iss. 1989. Cloning and molecular characterizationof geneswhose
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oyrcetracycline-fi
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MMHiney, C. O’Brien, R. Cope and P. Smith. 1995. Emergencein
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